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Review
. 2024 Aug 11;25(16):8751.
doi: 10.3390/ijms25168751.

Primary Progressive Multiple Sclerosis-A Key to Understanding and Managing Disease Progression

Izabela Sempik  1 , Edyta Dziadkowiak  2 , Helena Moreira  3 , Anna Zimny  4 , Anna Pokryszko-Dragan  2
Affiliations
Review

Primary Progressive Multiple Sclerosis-A Key to Understanding and Managing Disease Progression

Izabela Sempik et al. Int J Mol Sci. .

Abstract

Primary progressive multiple sclerosis (PPMS), the least frequent type of multiple sclerosis (MS), is characterized by a specific course and clinical symptoms, and it is associated with a poor prognosis. It requires extensive differential diagnosis and often a long-term follow-up before its correct recognition. Despite recent progress in research into and treatment for progressive MS, the diagnosis and management of this type of disease still poses a challenge. Considering the modern concept of progression "smoldering" throughout all the stages of disease, a thorough exploration of PPMS may provide a better insight into mechanisms of progression in MS, with potential clinical implications. The goal of this study was to review the current evidence from investigations of PPMS, including its background, clinical characteristics, potential biomarkers and therapeutic opportunities. Processes underlying CNS damage in PPMS are discussed, including chronic immune-mediated inflammation, neurodegeneration, and remyelination failure. A review of potential clinical, biochemical and radiological biomarkers is presented, which is useful in monitoring and predicting the progression of PPMS. Therapeutic options for PPMS are summarized, with approved therapies, ongoing clinical trials and future directions of investigations. The clinical implications of findings from PPMS research would be associated with reliable assessments of disease outcomes, improvements in individualized therapeutic approaches and, hopefully, novel therapeutic targets, relevant for the management of progression.

Keywords: biomarkers of progression; immune dysregulation; neurodegeneration; primary progressive multiple sclerosis; remyelination failure.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Background for disease progression in PPMS: (a) basic components, (b) key players involved in neuroinflammation and neurodegeneration.
Figure 1
Figure 1
Background for disease progression in PPMS: (a) basic components, (b) key players involved in neuroinflammation and neurodegeneration.
Figure 2
Figure 2
Patient with PPMS. MR images of the brain showing the following: (a) multiple demyelinating plaques in periventricular and juxtacortical (arrow) locations on FLAIR sequence, (b) cortical plaques (arrows) on DIR sequence and (c) a paramagnetic rim lesion (arrow) on SWI sequence; own resources.
Figure 3
Figure 3
Patient with PPMS. MR images of the spine showing: (a) multiple demyelinating plaques within the cervical spinal cord (arrows) on a sagittal fat-saturated T2 weighted image and (b) in the axial plane on a T2-weighted image (arrow). Fat-saturated T2-weighted image (c) showing atrophy of the lower thoracic spinal cord in the course of the disease (arrow); own resources.
See this image and copyright information in PMC

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